Tetra-modality bladder preservation with avelumab for muscle-invasive urothelial cancer: a phase II trial (TRIUMPH-B01).

Background/aims: Muscle-invasive bladder cancer (MIBC) has a 5-year survival rate of 40-60% following traditional treatment with neoadjuvant chemotherapy (NAC) and radical cystectomy (RC), which significantly impacts quality of life. Bladder preservation strategies, including maximal transurethral resection of the bladder tumor (TURBT), NAC, and radiation therapy, offer similar survival rates with better quality of life. Immune checkpoint inhibitors like avelumab show potential benefits when combined with bladder preservation modalities. This phase II randomized, non-comparative, double-arm, open-label, multicenter trial evaluates the efficacy and safety of two tetra-modality bladder preservation strategies in MIBC patients (T2-T4N0M0). The primary endpoint is the 2-year proportion of bladder-preserved participants. Secondary endpoints include response rates post-induction, quality of life, and safety evaluations.

Methods: Eighty participants will be randomized 1:1 into Arm A or Arm B. All participants will first receive induction chemotherapy (DDMVAC or GC) combined with avelumab, followed by disease evaluation using imaging and TURBT. Those achieving a complete or near-complete response will proceed to hypofractionated radiation therapy (55 Grays in 20 fractions). After radiation, Arm A will receive maintenance avelumab for 1 year, while Arm B will follow a watch-and-wait approach. Non-responders in both arms will be referred for salvage RC.

Clinical trial registration: NCT06686381 (ClinicalTrials.gov).